Tardive Dyskinesia: Treatment Update.

PURPOSE OF REVIEW: Tardive dyskinesia (TD) is caused by exposure to medications with dopamine antagonism, mainly antipsychotics. It often distresses individuals, physically and emotionally and affects their quality of life. We evaluated peer-reviewed recently published articles with a goal of providing a critically appraised update on the latest advancements in this field. RECENT FINDINGS: In 2017, FDA approved VMAT2 inhibitors, deutetrabenazine and valbenazine. They have demonstrated efficacy in several class 1 studies. Also there have been update in the evidence-based guidelines for treatment for tardive dyskinesia. Various medication classes are being used for treatment of TD with VMAT2 inhibitors to be first FDA-approved medications. Their use should be tailored to the individual patient. Long-term studies will further guide us in how to optimize treatment, especially in the real-world setting. As clinicians, we need to take into consideration all aspects of symptomatology, etiology, potential side effects of the medications, to find the best possible "match" for our patients.

Sphingosine-1-phosphate promotes the differentiation of adipose-derived stem cells into endothelial nitric oxide synthase (eNOS) expressing endothelial-like cells.

BACKGROUND: Adipose tissue provides a readily available source of autologous stem cells. Adipose-derived stem cells (ASCs) have been proposed as a source for endothelial cell substitutes for lining the luminal surface of tissue engineered bypass grafts. Endothelial nitric oxide synthase (eNOS) is a key protein in endothelial cell function. Currently, endothelial differentiation from ASCs is limited by poor eNOS expression. The goal of this study was to investigate the role of three molecules, sphingosine-1-phosphate (S1P), bradykinin, and prostaglandin-E1 (PGE1) in ASC endothelial differentiation. Endothelial differentiation markers (CD31, vWF and eNOS) were used to evaluate the level of ASCs differentiation capability. RESULTS: ASCs demonstrated differentiation capability toward to adipose, osteocyte and endothelial like cell phenotypes. Bradykinin, S1P and PGE were used to promote differentiation of ASCs to an endothelial phenotype. Real-time PCR showed that all three molecules induced significantly greater expression of endothelial differentiation markers CD31, vWF and eNOS than untreated cells. Among the three molecules, S1P showed the highest up-regulation on endothelial differentiation markers. Immunostaining confirmed presence of more eNOS in cells treated with S1P than the other groups. Cell growth measurements by MTT assay, cell counting and EdU DNA incorporation suggest that S1P promotes cell growth during ASCs endothelial differentiation. The S1P1 receptor was expressed in ASC-differentiated endothelial cells and S1P induced up-regulation of PI3K. CONCLUSIONS: S1P up-regulates endothelial cell markers including eNOS in ASCs differentiated to endothelial like cells. This up-regulation appears to be mediated by the up-regulation of PI3K via S1P1 receptor. ASCs treated with S1P offer promising use as endothelial cell substitutes for tissue engineered vascular grafts and vascular networks.

Does Extended Use of Clopidogrel-Based Dual Anti-Platelet Therapy Increase the Risk of Gastrointestinal Bleeding?

BACKGROUND: Clopidogrel-based dual anti-platelet therapy (CDAPT) has shown significant benefits in the management of coronary artery disease (CAD), up to 1-year duration. Gastrointestinal bleeding (GIB) is one of the limiting factors for prolonged use of CDAPT. METHODS: We identified all patients taking CDAPT from our ambulatory clinics. Demographic, clinical, laboratory and pharmacological data were abstracted. American Heart Association (AHA) guidelines were used to determine the duration of CDAPT therapy. The study population was divided into two groups based on the duration of therapy. Individuals who received CDAPT more than 12 months were deemed as extended use. RESULTS: A total of 351 patients with CAD were taking CDAPT. Majority of patients (276/351, 79%) were taking CDAPT beyond 1 year. There were no differences in baseline characteristics between the two groups. There was no significant difference in the incidence of GIB between the two groups. However, in subgroup analysis, there was a significant difference in the incidence of GIB in men. Men who were taking CDAPT beyond 12 months had almost three times higher incidence of GIB compared to those who were taking less than 12 months (25% vs. 8%, P = 0.04). The excess GIB in men prevailed despite adjusting for non-steroidal anti-inflammatory drugs (NSAIDs) or direct oral anticoagulant (DOAC) use. CONCLUSIONS: We found that a majority of patients were taking CDAPT beyond the recommended duration. We observed that men taking CDAPT for an extended duration had a three times higher incidence of GIB. It would be reasonable for physicians to be aware of the higher risk of GIB in men and carefully assess the risks and benefits of extended use of CDAPT.

Ramsay Hunt Syndrome with Multiple Cranial Neuropathy in an Human Immunodeficiency Virus (HIV) Patient.

BACKGROUND Ramsay Hunt syndrome is a rare otologic complication resulting from varicella zoster virus reactivation that can present with a myriad of clinical presentations. Most common being triad of ear pain, vesicles at auricle, and ear canal with same side facial palsy. CASE REPORT We report a case of a 29-year-old male with a human immunodeficiency virus (HIV) infection who presented with left facial palsy, vesicles, pain in the left ear, dysphagia, dizziness, and headache resulting from multiple cranial nerves involvement such as cranial nerve V, VII, VIII, IX, and X. CONCLUSIONS This case report raises awareness among general practitioners to investigate for Ramsay Hunt syndrome in HIV patients presenting with ear pain with a thorough neurological exam and emphasize on the interplay of different specialties in managing these patients.

A Rare Case of Necrotizing Myopathy and Fibrinous and Organizing Pneumonia with Anti-EJ Antisynthetase Syndrome and SSA Antibodies.

BACKGROUND Idiopathic inflammatory myopathies are autoimmune disorders that can involve the skin, joints, muscles, and lungs. The most common of these disorders are dermatomyositis, polymyositis, overlap syndrome, and inclusion body myositis. Necrotizing autoimmune myopathy is an idiopathic inflammatory myopathy that is rarely associated with Sjögren's syndrome. The most common lung findings associated with anti-EJ antisynthetase syndrome are nonspecific interstitial pneumonia and usual interstitial pneumonia; this condition is rarely associated with fibrinous and organizing pneumonia. CASE REPORT Here, we present a rare case of necrotizing myopathy and fibrinous and organizing pneumonia in a 34-year-old African American man with Sjögren's syndrome and anti-EJ antibodies. The patient's presenting symptoms were cough and proximal muscle weakness of the extremities. He had elevated serum creatine kinase level, aldolase level, and erythrocyte sedimentation rate. Myositis panel was positive for anti-EJ antibodies. Chest radiography was consistent with bilateral interstitial infiltrates. CT chest showed patchy bilateral infiltrates. Quadriceps muscle biopsy revealed widespread necrotic fibers and lung biopsy showed fibrinous and organizing pneumonia. The patient responded well to immunoglobulin therapy, mycophenolate, and prednisone, which resulted in complete resolution of bilateral infiltrates and improved muscle pain and weakness. CONCLUSIONS Myopathies are characterized by myalgia and muscle weakness due to muscle fiber dysfunction and are associated with autoimmune diseases. Histopathological features may differ in idiopathic inflammatory myopathies. It is important to recognize the rare association of anti-EJ autoantibodies with necrotizing myopathy and interstitial lung disease, which responds well to methylprednisolone and intravenous immunoglobulin.